Abstract Chronic liver injury due to alcohol, metabolic dysfunction, viral hepatitis, or autoimmune disease results in liver inflammation and fibrosis. Liver fibrosis will progress to cirrhosis which is estimated to affect 1?2% of the world?s population. The major clinical consequences of cirrhosis are liver failure and hepatocellular carcinoma (HCC), both of which increase the risk of death. Alcoholic liver disease (ALD) is a leading cause of liver disease and liver-related deaths globally, particularly in developed nations. The current gold standard diagnostic method, liver biopsy, has many limitations including sampling error and high inter-observer variability with a 33% error rate even for the diagnosis of advanced stages of liver fibrosis. In addition, liver biopsy is an invasive, painful and expensive procedure with the risk of complications involving hospitalization and mortality. Liver biopsy is therefore of limited use for screening or monitoring disease progression. None of several technologies investigated offers the desired sensitivity and specificity for the detection or staging of fibrosis. The novel contrast agent developed in our laboratory, ProCA32.Collagen1, combined with innovative processing techniques made possible by this agent, promise to significantly enhance the precision of MRI in diagnosing and monitoring liver fibrosis. We have successfully met all of the proposed aims and milestones for Phase I to obtain proof-of-principle evidence to achieve early detection of liver fibrosis with significantly improved sensitivity and selectivity. We have demonstrated that ProCA32.Collagen detects in vivo liver fibrosis in mouse models. In this Phase II project, we will optimize affinity for collagen binding and biodistribution and validate in vivo capability in the early detection and staging of liver fibrosis. We will obtain essential data required for filing IND applications leading to clinical translation.